Association of antipsychotic nonadherence with all-cause mortality in adults with schizophrenia newly treated or reinitiating antipsychotic medication: A retrospective healthcare claims study

Antipsychotic nonadherence is related to adverse outcomes in schizophrenia, including relapse and hospitalization; however, its impact on mortality remains unclear. This study evaluated associations between antipsychotic adherence levels and all-cause mortality using longitudinal claims data from the Optum Clinformatics® Data Mart Database. Eligible adults had ≥2 outpatient claims on separate dates or ≥1 inpatient claim with a schizophrenia diagnosis during the 12 months prior to/at index (i.e., antipsychotic initiation/reinitiation date) and no antipsychotic prescriptions or bipolar disorder diagnoses within 12 months pre-index. Medication adherence levels were defined by cumulative proportion of days covered (PDC): high adherence (≥0.8), low/moderate adherence (≥0.2 to <0.8), and nonadherence (<0.2). Adherence and all-cause mortality were evaluated during follow-up. A marginal structural model adjusting for baseline and time-varying confounding factors was used to estimate hazard ratios (HRs) and 95% CIs for mortality at different adherence levels. Of 6417 included adults (age=55.3 ± 20.5 years; males=54.0%; White=51.0%), the majority (81.7%) were prescribed second-generation oral antipsychotics at index. Within 6 months of antipsychotic initiation, mean cumulative PDC was 0.59±0.33. During a median follow-up of 17.3 months (interquartile range: 6.2-36.7), compared with high-adherent patients, all-cause mortality hazard was significantly greater in nonadherent (HR=1.80 [95%CI: 1.43-2.27]) and low/moderate-adherent (HR=1.53 [95% CI: 1.25-1.89]) patients. Five-year estimated survival rates were 67%, 71%, and 80% for nonadherent, low/moderate-adherent, and high-adherent patients, respectively. In this study, suboptimal antipsychotic adherence was associated with elevated mortality risk in patients with schizophrenia. Improved adherence may enhance survival and should be reinforced early in the disease course.